Since little is known regarding the etiologic role of the immune system in alcohol-induced liver injury, this proposal represents an attempt to define cellular, humoral, and serum factors which are operative during the disease process. We will compare these studies to other acute and chronic liver diseases to determine if there are unique abnormalities attributable to patients with alcoholic liver disease. We have demonstrated the presence of circulating immune complexes in patients with acute alcoholic hepatitis and now will examine their physical properties and antigenic composition. The search for tissue deposition in the liver is of critical importance. There are potent circulating inhibitory factors in the serum of patients with alcoholic hepatitis which dramatically influence the effector function of normal cells and we will further explore their physical-chemical properties and biological activity on autologous lymphocytes. Investigations will be initiated to examine the control of immunoglobulin synthesis in vitro which may provide new and important information on the mechanism(s) of hypergammaglobulinemia so often observed in these patients. Finally, we will study the effect(s) of acute and chronic ethanol intoxication on hepatic regeneration. In this regard both in vivo and in vitro systems will be employed to probe the control of DNA synthesis and the possible mechanisms of ethanol action on liver repair. Thus, one of the long-term goals of this research is to focus on the magnitude and rate of liver repair under experimental conditions. It is reasonable to suspect that ethanol may have similar inhibitory effects on the hepatocyte proliferation response in man.